This exploratory project will test a hypothesis that the high-frequency signal (HFS) we have recently observed during interictal spikes in infants with epilepsy is a biomarker of epileptogenesis. Based on their human and animal studies, Engel and others at UCLA have proposed that an HFS in the range of 250-500 Hz, the so- called fast ripple (FR), superimposed on interictal spikes is a biomarker of epileptogenesis in adults with mesial temporal lobe epilepsy. Finding a biomarker of epileptogenesis is important since this would enable a clinician to identify areas eventually capable of producing seizures. Unfortunately, this FR from the mesial temporal lobe does not appear to be detectable over the scalp with magnetoencephalography (MEG) or electroencephalography (EEG) according to the intracranial data of Gotman and his coworkers from epilepsy patients. It is still unknown whether the FR is a biomarker of epileptogenesis in neocortical epilepsy in adults. Here we focus on epilepsy in infants since this is the population that can benefit most from such a biomarker. Since many types of infantile epilepsy is neocortical in origin, an analog of FR should be more easily detectable. We have recently developed a new MEG instrument called babySQUID that is optimized for measuring cortical activity in infants. Because its magnetic field sensing coils are much closer to the scalp than the coils of conventional MEG systems (6 vs 20 mm) and the scalp and skull of infants are thin, much weaker neocortical signals are measurable. Therefore, we have looked for an analog of FR in infants using the babySQUID in our preliminary study and found that there is an HFS in the range of 70-120 Hz, which is present only in some interictal spikes identified in some patients with epilepsy and not observed in continuous recordings from normal controls in a similar age range. This HFS shows polarity reversal over a cluster of sensing coils, indicating that it was cortical in origin. Our specific aim is to test whether this HFS is associated with electrographic signs of seizure since that is the first step in establishing the HFS as a possible biomarker. Since the electrographic activity is not always accompanied by behavioral seizures in infants, it can be measured using MEG without movement artifacts. We will study <3 year old infants for the presence of the HFS and, if found, we will test if the locations of its generator and the seizure generator coincide. We also predict that the seizure site will not coincide with locations of interictal spikes without HFS. Age matched normal controls will be studied to ascertain that the HFS is characteristic of epilepsy. If successful, this research will open new possibilities for the prevention and treatment of epilepsy in infants before epilepsy causes irreparable damage in a wide region of the brain, leading to general cognitive decline.Relevance: Identification of a biomarker for epileptogenesis associated with interictal spikes in infants has the potential to provide a noninvasive method for determining the site of seizure onset in young infants. This could significantly decrease the risk associated with invasive diagnosis, while at the same time providing information to better direct the course of treatment at a time when the brain is most able to fully recover and possibly lead to a normal outcome for the child.